1. Structural Biology and Molecular Biophysics
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HDX-MS reveals nucleotide-based, anti-correlated opening and closure of SecA/ SecY channels of the bacterial translocon

  1. Zainab Ahdash
  2. Euan Pyle
  3. William John Allen
  4. Robin A Corey
  5. Ian Collinson  Is a corresponding author
  6. Argyris Politis  Is a corresponding author
  1. King's College London, United Kingdom
  2. University of Bristol, United Kingdom
  3. University of Oxford, United Kingdom
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Cite this article as: eLife 2019;8:e47402 doi: 10.7554/eLife.47402

Abstract

The bacterial Sec translocon is a multi-protein complex responsible for translocating diverse proteins across the plasma membrane. For post-translational protein translocation, the Sec-channel - SecYEG - associates with the motor protein SecA to mediate the ATP-dependent transport of pre-proteins across the membrane. Previously, a diffusional based Brownian ratchet mechanism for protein secretion has been proposed [Allen et al. eLife 2016;5:e15598]; the structural dynamics required to facilitate this mechanism remain unknown. We employ hydrogen-deuterium exchange mass spectrometry (HDX-MS) to reveal striking nucleotide-dependent conformational changes in the Sec protein-channel from Escherichia coli. In addition to the ATP-dependent opening of SecY, reported previously, we observe a counteracting, and ATP-dependent, constriction of SecA around the pre-protein. ATP binding causes SecY to open and SecA to close; while, ADP produced by hydrolysis, has the opposite effect. This alternating behaviour could help impose the directionality of the Brownian ratchet for protein transport through the Sec machinery.

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Author details

  1. Zainab Ahdash

    Department of Chemistry, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4495-8689
  2. Euan Pyle

    Department of Chemistry, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4633-4917
  3. William John Allen

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9513-4786
  4. Robin A Corey

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1820-7993
  5. Ian Collinson

    School of Biochemistry, University of Bristol, Bristol, United Kingdom
    For correspondence
    ian.collinson@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3931-0503
  6. Argyris Politis

    Department of Chemistry, King's College London, London, United Kingdom
    For correspondence
    argyris.politis@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6658-3224

Funding

Wellcome (109854/Z/15/Z)

  • Argyris Politis

Medical Research Council (MC_PC_15031)

  • Argyris Politis

Biotechnology and Biological Sciences Research Council (BB/N015126/1)

  • Ian Collinson

Biotechnology and Biological Sciences Research Council (BB/M003604/1)

  • Ian Collinson

Biotechnology and Biological Sciences Research Council (BB/I008675/1)

  • Ian Collinson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Yibing Shan, DE Shaw Research, United States

Publication history

  1. Received: April 4, 2019
  2. Accepted: July 9, 2019
  3. Accepted Manuscript published: July 10, 2019 (version 1)

Copyright

© 2019, Ahdash et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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